The present invention relates to a process for preparing aromatic or heteroaromatic nitrites by cyanating the corresponding aryl halides in the presence of copper catalysts and potassium hexacyanoferrate(II) (K4[Fe(CN)6]) or potassium hexacyanoferrate(III) (K3[Fe(CN)6]).
Aromatic and heteroaromatic nitriles are of industrial significance as fine chemicals, and agrochemical and pharmaceutical intermediates. Processes for their preparation are therefore of industrial significance. A known method employed on the industrial scale for preparing aromatic nitrites is the ammoxidation of substituted toluenes. This process is, however, usable practically only when the corresponding starting materials (toluenes) are available inexpensively. In addition, the ammoxidation does not succeed in the presence of oxidation-sensitive substituents in the substrate. Further technical processes for preparing benzonitriles are reactions of carboxylic acids and ammonium salts or amides by distillation with strongly water-binding substances (e.g. P2O5) and reaction of carboxylic acids or esters in the vapour phase with ammonia over an Al fixed bed at 500° C. However, such processes have disadvantages owing to the severe reaction conditions and generally cannot be applied to complexes of substituted aromatic nitrites.
Alternative inexpensive starting materials for aromatic nitrites are the corresponding aryl chlorides and bromides. However, the substitution of the halide by cyanide by known processes usually succeeds only unsatisfactorily. For example, aromatic halides react with HCN in the vapour phase at 650° C. or at 480-650° C. in the presence of a metal catalyst or metal oxide catalyst. Catalysts which accelerate the reaction of aryl halides with cyanide under milder reaction conditions are palladium complexes, nickel complexes and copper complexes. For instance, R. Breitschuh, B. Pugin, A. Indolese and V. Gisin (EP 0 787 124 B1 and U.S. Pat. No. 5,883,283) describe the preparation of substituted 3-aminobenzonitriles from the corresponding substituted 3-aminochlorobenzenes in the presence of preferably Ni complexes and stoichiometric amounts of a complexing salt. Disadvantages in this process are the use of an excess of reducing agent and the restriction of the reaction to a specific substrate class.
B. R. Cotter (U.S. Pat. No. 4,211,721) describes the positive influence of ether components from the group of 18-crown-6, polyethers, alkoxy polyethers or mixtures thereof with a molar mass of 200-25 000 as a cocatalyst on the palladium-catalysed cyanation of aryl halides.
J. B. Davison, R. J. Jasinski and P. J. Peerce-Landers (U.S. Pat. No. 4,499,025) describe the preparation of aromatic nitrites from chloroaromatics, catalysed by a group VIII metal(0) complex which is formed electrochemically. However, this procedure is exceptionally expensive in comparison to conventional batch processes.
M.-H. Rock and A. Marhold (DE 197 06 648 A1 and WO 98/37 058) describe the preparation of aromatic nitrites from chloroaromatics in the presence of a nickel catalyst and of a ketone by reaction with cyanides. The reaction can, however, be performed successfully only when the cyanide concentration is controlled strictly, since the catalyst is otherwise cyanated irreversibly. A disadvantage in this process is again the need to add a reducing agent such as zinc and the use of specific ketones as solvents.
M. Beller and co-workers describe the influence of crown ethers, diphosphine ligands and diamine ligands on the palladium-catalysed reaction of aryl halides with alkali metal cyanides (DE 101 13 976, Tetrahedron Lett. 2001, 42, 6707-10). Based on these studies, processes have been developed which are based on metered addition of acetone cyanohydrin (Angew. Chem. 2003, 115, 1700-3), trimethylsilyl cyanide (J. Organomet. Chem. 2003, 684, 50-5) or hydrocyanic acid (DE 103 22 408.4) as the cyanide donor. A disadvantage here is the use of expensive palladium catalysts and specific ligands.
A. Viauvy and M. Casado (EP 0 004 099 A1), moreover, describe the reaction of chloroaromatics to give the corresponding nitrile with stoichiometric amounts of copper cyanide and a bromide source or alkali metal cyanide or tetraalkylammonium cyanide in the presence of copper bromide and a phase transfer catalyst or copper cyanide and lithium iodide. A disadvantage here is the use of stoichiometric amounts of the transition metal.
A copper-catalysed cyanation of aryl halides has been described by Wu et al. (Tetrahedron Lett. 2002, 43, 387-389). They use 5 mol % of a copper(I) salt as a catalyst and sodium cyanide as the cyanide source. Good yields can be achieved, however, only in the reaction of reactive and expensive iodoaromatics. A further disadvantage of the process is the use of ionic liquids as the solvent, which are expensive and can be cleaned only with difficulty.
J. Zanon, A. Klapars and S. L. Buchwald (J. Am. Chem. Soc. 2003, 125, 2890-1) describe the cyanation of bromoaromatics with sodium cyanide in the presence of 10 mol % of copper(I) iodide as a catalyst and 20 mol % of potassium iodide as a cocatalyst. In addition, one equivalent of N,N′-dimethylethylenediamine is added. It is assumed that the aryl bromides are converted to the corresponding iodides as an intermediate, which are then cyanated.
In a method likewise catalysed by copper(I) iodide of Cristau et al. (Chem. Eur. J. 2005, 11, 2483-2492), 20 mol % of the 1,10-phenanthroline ligand and acetone cyanohydrin as the cyanide donor are used. Here too, potassium iodide has to be used as a cocatalyst.
A significant disadvantage of all catalytic cyanations described so far is the sometimes extremely high toxicity of the cyanating agents used, which is based on the fact that hydrocyanic acid is released on contact with water. M. Beller et al. for the first time described catalytic cyanations with the non-toxic potassium hexacyanoferrate(II) [Chem. Commun. 2004, 1388-1389]. However, a disadvantage in this process is that the reactions succeed only in conjunction with a palladium catalyst.
Moreover, T. Schareina, A. Zapf and M. Beller (Tetrahedron Lett. 2005, 46, 2585-2588) describe the cyanation of aryl bromides with Cu catalysts in the presence of the N,N′-dimethylethylenediamine ligand. Owing to the high cost of this ligand, industrial uses are unrealistic.
In summary, it remains to be emphasized that almost all transition metal-catalysed cyanations of aryl halides known to date use either expensive toxic cyanide sources or expensive catalyst systems.